Abstract

Question

In patients with nonulcer dyspepsia, how effective is Helicobacter pylori therapy in reducing symptoms?

Data sources

Studies were identified by searching MEDLINE and HealthSTAR (1984 to 1999); reviewing
proceedings from the annual meetings of the American Gastroenterological Association,
the American College of Gastroenterology, and the European H. pylori Study Group from 1995 to 1999; reviewing the bibliographies of relevant papers; and
contacting manufacturers of medications for H. pylori and experts in the field (no additional studies were identified in this manner).

Study selection

Studies were selected if they were randomized controlled trials evaluating the effectiveness
of combination therapy for H. pylori in patients with nonulcer dyspepsia and H. pylori infection. The trials had to have at least 1 month of follow-up after the end of therapy
and had to assess symptoms of nonulcer dyspepsia.

Data extraction

Main results

10 studies met the selection criteria. The primary outcome was greater treatment success
with H. pylori eradication therapy than with control therapy. 7 studies provided data on the proportion
of patients who had treatment success in the treatment and control groups at least
1 month after completion of H. pylori eradication therapy. Success rates were similar in the 2 groups (Table), but heterogeneity
was present. Heterogeneity resolved with the exclusion of 1 trial, but the difference
in treatment success was still statistically nonsignificant. Success rates between
the groups did not differ when only those trials that used a specifically stated definition
of dyspepsia were combined or when only those trials in which treatment resulted in
cure rather than persistent infection were combined.

Conclusion

Helicobacter pylori therapy in patients with nonulcer dyspepsia and Helicobacter pylori infection does not reduce symptoms.

*Abbreviations defined in Glossary; RBI, NNT, and CI calculated from data in article.

Commentary

Over the past 3 years, a number of large, high-quality studies have investigated the
role of H. pylori eradication in nonulcer dyspepsia. Most, with 1 notable exception, have found no significant
benefit, but small differences in response rates have encouraged the use of meta-analysis.
The most recent high-quality meta-analysis found a small but significant benefit over
placebo (1). Laine and colleagues' analysis found no benefit but omitted 4 studies included
in the previous meta-analysis and included 5 previously excluded. In particular, the
largest study by Malfertheiner and colleagues (2) was excluded. This study has only been published in abstract form but was probably
excluded by failing to provide an adequate definition of treatment success. The results
of this trial, however, strongly influenced the outcome of the earlier meta-analysis
and explain the main difference in outcome.

Without a uniformly agreed-upon disease definition, outcome measure, or trial duration,
and with innumerable possible treatment regimens, it is not surprising that different
meta-analyses include different trials and have different outcomes. Of the 5 studies
common to both analyses, only 1 showed a statistically significant benefit over placebo,
but all but 1 had a greater proportion of patients who responded in the active-treatment
group. Most studies chose a primary outcome of symptom resolution, which is better
defined and easier to compare between studies but obscures the fact that, even in
the positive study, mean symptom scores were comparable between the 2 groups.

The contradictory results of the different trials and analyses say more about the
heterogeneity of the disorder than they do about the quality of the trials. Few would
argue that H. pylori can have more than a minor role in dyspepsia. Treatment seems to benefit most populations
with a high background ulcer rate. We know that about 5% of H. pylori-infected persons develop an ulcer each year, and this rate may be higher in some
populations. These patients would be classified as having nonulcer dyspepsia at screening,
but they could then surreptitiously benefit from eradication by avoiding an ulcer.